A Two-Wave Molecular Mechanism for Endometriosis Disease Progression

The authors of this literature review believe that the development of Endometriosis can be explained by a two part process where bacterial infection is followed by sterile inflammation.

Key Points

Highlights:

• This literature review hopes to elucidate the molecular mechanism that governs the pathogenesis of endometriosis. The authors of the study propose a two-wave mechanism that includes non-specific bacterial infection and sterile inflammation.

Importance:

• Understanding the development of the disease, especially at the molecular level, will allow research to progress such that targeted therapies can be created for those suffering from this illness.

What’s done here?

• The authors of this literature review used electronic databases to find English-language studies that are pertinent to the topic at hand.

Key results:

• The first wave of disease development is the non-specific bacterial infection, which takes place in the uterine endometrium and peritoneal fluid. Intrauterine microbes are thought to emit stimuli that activate pathogen recognition receptors. These receptors then go on to activate pro-inflammatory pathways and innate immunity.
• The second wave of disease development is the sterile inflammation and this wave has multiple components. It is important to note that both of these components are bidirectional processes that cause the persistent sterile inflammation and anti-apoptosis. The first component is oxidative stress, which is caused by the influx of iron that occurs in retrograde menstruation. The second component is danger-associated molecular patterns (DAMP)‐mediated danger signals. DAMPs are released from damaged cells and are detected by Toll-like receptors. It is believed that DAMPs are associated with nuclear transcription factor-κB-dependent sterile inflammation and can cause more tissue destruction and oxidative stress.

Limitations of the study:

• Since this is a literature review and not an experiment in itself, the limitations lie in the fact that the authors of the review must rely on the results of other studies in order to reach certain conclusions. Additionally, conclusions that are reached are not tested for further accuracy.

Lay Summary

Kobayashi et al. recently published a review paper in Molecular Medicine Reports titled “Pathogenesis of endometriosis: The role of initial infection and subsequent sterile inflammation,” which discusses at length the role of non-specific bacterial infection and sterile inflammation in the disease progression of endometriosis.

After reviewing various English-language publications on the subject, the authors use epidemiological and experimental data to propose a two-wave mechanism for the pathogenesis of endometriosis. The first wave of development occurs within the uterine endometrium and peritoneal fluid. It is thought that intrauterine microbes emit stimuli that activate pathogen recognition receptors, which subsequently activate pro-inflammatory pathways and innate immunity. The next wave of disease development is split into two separate steps, both of which are bidirectional processes that cause the persistent sterile inflammation and anti-apoptosis: oxidative stress and danger-associated molecular patterns (DAMP)‐mediated danger signals. Retrograde menstruation involves an influx of iron and secondary to this overall process is oxidative stress. The second step of the second wave involves Toll-like receptors that recognize DAMPs, which are released from damaged cells and are thought to be a part of nuclear transcription factor-κB-dependent sterile inflammation. Upon release, DAMPs can create more tissue destruction, sterile inflammation, and oxidative stress.

It is important to note that this is merely a summary of a detailed review article, those interested in learning more should refer to the article itself.

Research Source: https://www.spandidos-publications.com/mmr/9/1/9